1887

Abstract

The ORF designated HI1275 in the Rd KW20 genomic sequence encodes a putative -adenosyl methyltransferase with significant similarity to tellurite-resistance determinants () in other species. While the . can complement an mutation, thus restoring tellurite resistance, its role in is unknown. In a previous study defining the iron and haem modulon of , we showed that transcription of this gene in Rd KW20 increases during growth in iron- and haem-restricted media. Since iron and haem uptake genes, and other known virulence factors, constitute the majority of the iron- and haem-regulated gene set, we postulated that may play a role in nutrient acquisition and/or the virulence of . A mutant was constructed in the type b strain 10810 and was evaluated for growth defects in various supplemented media, as well as for its ability to cause infection in rat models of infection. Deletion of leads to an increase in sensitivity both to tellurite and to the oxidizing agents cumene hydroperoxide, tert-butyl hydroperoxide and hydrogen peroxide. The mutant additionally showed a significantly reduced ability to utilize free haem as well as several haem-containing moieties including haem–human serum albumin, haemoglobin and haemoglobin–haptoglobin. Examination of the regulation kinetics indicated that transcription of was independent of both tellurite exposure and oxidative stress. Paired comparisons of the mutant and the wild-type strain 10810 showed that is required for wild-type levels of infection in rat models of invasive disease. To our knowledge this is the first report of a role for in virulence in any bacterial species. These data demonstrate that plays a role in both resistance to oxidative damage and haem uptake/utilization, protects from tellurite exposure, and is important for virulence of this organism in an animal model of invasive disease.

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2010-04-01
2020-01-23
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